SNPs in the exons of Toll-like receptors are associated with susceptibility to type 1 diabetes in Chinese population

Chengjun Sun; Dijing Zhi; Shuixian Shen; Feihong Luo; Carani B Sanjeevi

doi:10.1016/j.humimm.2014.09.008

SNPs in the exons of Toll-like receptors are associated with susceptibility to type 1 diabetes in Chinese population

Hum Immunol. 2014 Nov;75(11):1084-8. doi: 10.1016/j.humimm.2014.09.008. Epub 2014 Sep 26.

Authors

Chengjun Sun¹, Dijing Zhi², Shuixian Shen², Feihong Luo³, Carani B Sanjeevi⁴

Affiliations

¹ Department of Medicine (Solna), Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Pediatric Endocrinology and Inherited Metabolic Disease, Children's Hospital of Fudan University, Shanghai, China.
² Department of Pediatric Endocrinology and Inherited Metabolic Disease, Children's Hospital of Fudan University, Shanghai, China.
³ Department of Pediatric Endocrinology and Inherited Metabolic Disease, Children's Hospital of Fudan University, Shanghai, China. Electronic address: luofh@fudan.edu.cn.
⁴ Department of Medicine (Solna), Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: sanjeevi.carani@ki.se.

PMID: 25261617
DOI: 10.1016/j.humimm.2014.09.008

Abstract

Objective: Toll-like receptors (TLRs) recognize a wide range of pathogen-associated molecular patterns (PAMP) and mount the initiation of immune response. Single nucleotide polymorphisms (SNPs) in exons of genes encoding TLRs might be responsible for the generation of an abnormal immune response which could lead to autoimmune diseases. In this study, we investigated the SNPs in TLRs in a Chinese population, and we hypothesized that SNPs in TLRs are associated with type 1 diabetes (T1D), an autoimmune disease caused by destruction of insulin producing pancreatic β-cells, in the studied population.

Research design and methods: We selected 28 SNPs in exons of TLRs with an aim to identify those that might have a direct correlation with T1D etiology and many have not been included in previous GWAS studies. Genotyping of those SNPs in TLRs was performed in 429 T1D patients and 300 age and gender-matched healthy controls in Chinese Han population which was not included in the earlier GWAS studies.

Results: Among the SNPs genotyped, the T allele of TLR1-626 was positively associated with T1D (OR=1.98, Pc=0.01). We identified another T1D association locus in TLR6: the homozygous AA genotype of TLR6-1329 was negatively and heterozygous GA was positively associated with T1D (OR=0.54, Pc=0.02 and OR=1.70, Pc=0.03, respectively). We also identified the haplotype T-G-A in TLR1 gene to be positively associated with T1D (OR=2.22, Pc=0.03). Additional haplotypes in TLR-6 also showed significant positive and negative association. In addition, our haplotype analysis and conditional analysis showed that these two SNPs are the primary T1D associated loci among the SNPs tested in our cohort in each TLR gene.

Conclusion: SNPs and haplotypes in TLR1 and TLR6 gene were associated with T1D in Chinese Han population. Our study, for the first time, indicates that TLR1 and TLR6 gene might play important roles in the etiology of T1D.

Keywords: Chinese; SNP; TLR; Type 1 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Asian People
Case-Control Studies
Child
Diabetes Mellitus, Type 1 / ethnology
Diabetes Mellitus, Type 1 / genetics*
Diabetes Mellitus, Type 1 / pathology
Exons*
Female
Gene Expression
Genetic Predisposition to Disease*
Haplotypes
Heterozygote
Homozygote
Humans
Linkage Disequilibrium
Male
Polymorphism, Single Nucleotide*
Toll-Like Receptor 1 / genetics*
Toll-Like Receptor 6 / genetics*

Substances

TLR6 protein, human
Toll-Like Receptor 1
Toll-Like Receptor 6